A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED)

Multicenter, Double-Blind, Randomized, Dose Ranging Study to Compare the Safety and Activity of MK0518 Plus Tenofovir and Lamivudine (3TC) Versus Efavirenz Plus Tenofovir and Lamivudine (3TC) in ART-Naive, HIV-Infected Patients

This is a study that will investigate the safety and efficacy of an investigational drug in Human immunodeficiency virus (HIV) infected patients.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome
• Intervention / Treatment: Drug: Comparator: MK0518 monotherapy; Drug: Placebo monotherapy; Drug: Comparator: MK0518 combination therapy; Drug: Comparator: tenofovir; Drug: Comparator: lamivudine; Drug: Comparator: efavirenz

Detailed Description

Participants who completed 48 weeks of the original 48-week double-blind study were invited to continue in two extensions: MK0518-004-10 (NCT00100048), which extended the study to 144 weeks, and MK0518-004-20 (NCT00100048), which extended the study to 240 weeks. Participants who had been randomized to MK0518 in the base study continued at 400 mg MK0518 twice daily.

Participants randomized to efavirenz in the base study continued to receive efavirenz at the dosage given in the base study. The doses of open label tenofovir and lamivudine continued unchanged.

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient must be HIV positive who must have received less than 7 days total of any antiretroviral therapy (HIV related therapy)

Extension Studies:

• First extension: Patient completed the 48-week base study
• Second extension: Patient completed the first 144-week extension study

Exclusion Criteria:

• Less than 18 years of age
• Individuals who currently do not test positive for HIV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 600 mg monotherapy; MK0518 600 mg twice daily	Drug: Comparator: MK0518 monotherapy; MK0518 twice daily for 10 days
Experimental: 400 mg monotherapy; MK0518 400 mg twice daily	Drug: Comparator: MK0518 monotherapy; MK0518 twice daily for 10 days
Experimental: 200 mg monotherapy; MK0518 200 mg twice daily	Drug: Comparator: MK0518 monotherapy; MK0518 twice daily for 10 days
Experimental: 100 mg monotherapy; MK0518 100 mg twice daily	Drug: Comparator: MK0518 monotherapy; MK0518 twice daily for 10 days
Placebo Comparator: placebo monotherapy; Placebo to MK0518 twice daily	Drug: Placebo monotherapy; Placebo to MK0518 twice daily
Experimental: 600 mg combo therapy; MK0518 600 mg + tenofovir + lamivudine	Drug: Comparator: MK0518 combination therapy; MK0518 twice daily for 48 weeks; Drug: Comparator: tenofovir; tenofovir 300 mg daily for 48 weeks; Drug: Comparator: lamivudine; lamivudine 300 mg daily for 48 weeks
Experimental: 400 mg combo therapy; MK0518 400 mg + tenofovir + lamivudine	Drug: Comparator: MK0518 combination therapy; MK0518 twice daily for 48 weeks; Drug: Comparator: tenofovir; tenofovir 300 mg daily for 48 weeks; Drug: Comparator: lamivudine; lamivudine 300 mg daily for 48 weeks
Experimental: 200 mg combo therapy; MK0518 200 mg + tenofovir + lamivudine	Drug: Comparator: MK0518 combination therapy; MK0518 twice daily for 48 weeks; Drug: Comparator: tenofovir; tenofovir 300 mg daily for 48 weeks; Drug: Comparator: lamivudine; lamivudine 300 mg daily for 48 weeks
Experimental: 100 mg combo therapy; MK0518 100 mg + tenofovir + lamivudine	Drug: Comparator: MK0518 combination therapy; MK0518 twice daily for 48 weeks; Drug: Comparator: tenofovir; tenofovir 300 mg daily for 48 weeks; Drug: Comparator: lamivudine; lamivudine 300 mg daily for 48 weeks
Active Comparator: EFV combo therapy; efavirenz + tenofovir + lamivudine	Drug: Comparator: tenofovir; tenofovir 300 mg daily for 48 weeks; Drug: Comparator: lamivudine; lamivudine 300 mg daily for 48 weeks; Drug: Comparator: efavirenz; efavirenz 600 mg every night at bedtime for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) on Day 10 (Cohort I)	Mean change from baseline on Day 10 in plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) (copies/mL)	Baseline and Day 10
Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I)	An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product. Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose.	10 days
Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II)		Week 24
Number of Patients With Clinical Adverse Experiences (CAEs)	An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product.	48 weeks
Number of Patients With Serious CAEs (Cohort I and II Combined)	Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose	48 weeks
Number of Patients With Serious CAEs and Non-serious CAEs at Week 144	An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product	144 Weeks
Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs)	An AE was defined as any unfavorable & unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to its use. Any worsening of a preexisting condition which was temporally associated with the use of the study drug, was also an AE. A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was cancer, or was an overdose.	Week 240
Number of Participants With HIV RNA (Human Immunodeficiency Virus Ribonucleic Acid) Levels Below 50 Copies/mL at Week 240	HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ UltraSensitive Assay.	Week 240

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II)		Week 24
Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II)	Mean change from baseline at Week 24 in plasma HIV RNA (copies/mL)	Baseline and Week 24
Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II)	Mean change from baseline at Week 24 in CD4 Cell Count (cells/mm3)	Baseline and Week 24
Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96		96 Weeks
Change From Baseline in Plasma HIV RNA at Week 96		Baseline and Week 96
Change From Baseline in CD4 Cell Count at Week 96		Baseline and Week 96
Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240	HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.	Week 240
Change From Baseline in Plasma HIV RNA at Week 240	HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.	Baseline and Week 240
Change From Baseline in CD4 (T-helper) Cell Count at Week 240	Change in number of CD4 cells/mm^3 from baseline to Week 240.	Baseline and Week 240

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 48		48 weeks
Number of Patients With Drug-related CAEs	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs	48 weeks
Number of Patients With Serious Drug-related CAEs	Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose. Drug-related are as assessed by an investigator who is a qualified physician according to his/her best clinical judgment.	48 Weeks
Number of Patients That Discontinued With CAEs		48 Weeks
Number of Patients With Laboratory Adverse Experiences (LAEs)	A laboratory adverse experience (LAE) is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product	48 Weeks
Number of Patients With Serious LAEs	Serious LAEs are any LAEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose	48 Weeks
Number of Patients With Drug-related LAEs	Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs	48 Weeks
Number of Patients With Serious Drug-related LAEs	Serious LAEs are any LAEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose	48 Weeks
Number of Patients That Discontinued With LAEs		48 Weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. doi: 10.1097/QAI.0b013e31802b4956. Erratum In: J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):492.
• Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Campbell H, Strohmaier KM, Wan H, Danovich RM, Teppler H; Protocol 004 Part II Study Team. Sustained antiretroviral effect of raltegravir after 96 weeks of combination therapy in treatment-naive patients with HIV-1 infection. J Acquir Immune Defic Syndr. 2009 Nov 1;52(3):350-6. doi: 10.1097/QAI.0b013e3181b064b0.
• Murray JM, Emery S, Kelleher AD, Law M, Chen J, Hazuda DJ, Nguyen BY, Teppler H, Cooper DA. Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase. AIDS. 2007 Nov 12;21(17):2315-21. doi: 10.1097/QAD.0b013e3282f12377.
• Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Gilde LR, Wan H, Miller MD, Wenning LA, Teppler H; Protocol 004 Part II Study Team. Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):125-33. doi: 10.1097/QAI.0b013e318157131c.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: December 22, 2004
• First Submitted That Met QC Criteria: December 22, 2004
• First Posted (Estimate): December 23, 2004

Study Record Updates

• Last Update Posted (Estimate): September 9, 2015
• Last Update Submitted That Met QC Criteria: September 4, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Integrase Inhibitors; Integrase Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Raltegravir Potassium; Lamivudine; Efavirenz
• Other Study ID Numbers: 0518-004; 2004_096